The purpose of this project is to gather clinical and molecular genetic information from extended, highly informative families ascertained through well-diagnosed and well-characterized probands, in order to investigate, on a case to case basis, the role of genetics in the etiology of the major psychotic illness's. Specific Aims: 1) To systematically collect clinical and history data and blood samples for molecular genetic analysis. A sequential sampling design will be used to obtain the extended family information needed to address multiple hypotheses related to genetic etiology, anticipation and parent-of-origin effects. 2) To utilize clinical and laboratory data to search for evidence of susceptibility regions for bipolar disorder and schizophrenia. Linkage analysis will be utilized to assess previously implicated loci for possible confirmation, and to identify novel regions, both by consideration of candidate genes, and via a global genome search using a two-stage design. 3) To apply state of the art statistical genetic methods in order to assess genetic contributions to the complex etiology of bipolar disorder and schizophrenia, including possible anticipation and parent-of-origin effects.